Abstract
Oxidative stress to dopaminergic neurons is believed to be one of the causes of neurodegeneration in Parkinson's disease (PD). It was investigated whether N-acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) have a preventive effect in an oxidative stress-induced model of PD. We found that NAC and OTC prevent degradation of PARP during auto-oxidized dopamine- or auto-oxidized L-DOPA-induced apoptosis in PC12 cells. In an animal model study, NAC and OTC showed a preventive effect against MPTP-induced loss of tyrosine hydroxylase-positive neurons, and suppressed the nuclear translocation of c-jun N-terminal kinase (JNK), suggesting that NAC and OTC can prevent MPTP-induced apoptosis by suppressing JNK activation. Therefore, these results suggest that NAC and OTC can be used as potential agents to prevent the progression of PD.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylcysteine / therapeutic use*
-
Analysis of Variance
-
Animals
-
Antioxidants / therapeutic use*
-
Blotting, Western / methods
-
Brain / drug effects
-
Brain / metabolism
-
Brain / pathology
-
Cell Count
-
Cell Death / drug effects
-
Disease Models, Animal
-
Dopamine / metabolism
-
Dopamine Agents / toxicity
-
Dose-Response Relationship, Drug
-
Drug Interactions
-
Immunohistochemistry / methods
-
JNK Mitogen-Activated Protein Kinases
-
MPTP Poisoning / prevention & control*
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mitogen-Activated Protein Kinases / metabolism
-
PC12 Cells
-
Pyrrolidonecarboxylic Acid
-
Rats
-
Thiazoles / therapeutic use*
-
Thiazolidines
-
Time Factors
-
Tyrosine 3-Monooxygenase / metabolism
Substances
-
Antioxidants
-
Dopamine Agents
-
Thiazoles
-
Thiazolidines
-
Tyrosine 3-Monooxygenase
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases
-
Pyrrolidonecarboxylic Acid
-
Dopamine
-
Acetylcysteine
-
2-oxothiazolidine-4-carboxylic acid